Novel agents for the treatment of multiple myeloma

Multiple myeloma is the second most common hematologic malignancy that remains incurable in the majority of patients. However, due to a better understanding of disease biology and pathogenesis much progress has been made with regard to treatment approaches in the past two decades. The proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiD) thalidomide and lenalidomide have been the first new drugs which have joined the traditional armamentarium consisting of glucocorticoids, alkylating agents and anthracyclines more than ten years ago and which have led to a survival advantage for the first time since the introduction of high dose chemotherapy and autologous hematopoietic stem cell transplantation. With the EMA approval of pomalidomide (IMiD) in August 2013 and the proteasome inhibitors carfilzomib in November 2015 and ixazomib in November 2016 the spectrum of the new drugs has been extended. In addition, new dasses of drugs have enriched tremendously the treatment options in the past two years. In August 2015, the first histone deacetylase inhibitor pano- binostat has been approved, followed by two monoclonal antibodies in May 2016: elotuzumab (directed against CS-1/SLAMF7) and daratumumab (directed against CD38). This article presents an overview about the mode of action, medical indication and side effects of the novel agents, including a summarization of clinical data of major studies focusing on the most recently approved drugs for the treatment of multiple myeloma.